SNAP-annotated 5mC-DNA-protein interactions: PDB entry 3fde

PDB-id

3fde; DSSR-derived features in text and JSON formats; DNAproDB

Class

ligase

Method

X-ray (1.41 Å)

Summary

Mouse uhrf1 sra domain bound with hemi-methylated cpg DNA, crystal structure in space group c222(1) at 1.4 Å resolution

Reference

Hashimoto H, Horton JR, Zhang X, Cheng X (2009): "UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications." Epigenetics, 4, 8-14.

Abstract

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication.

• The contacts include paired nucleotides (mostly a G in Watson-Crick G-C pairing) and amino-acids within a 4.5-Å distance cutoff to base atoms of 5mC.
• The structure is oriented in the base reference frame of 5mC, allowing for easy comparison and direct superimposition between entries.
• The black sphere (•) denotes the 5-methyl carbon atom in 5mC.